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Acute viral hepatitis. The clinical course of acute hepatitis is always the same. There’s a fever, arthritis, and a rash in a small percentage of viral prodrome, and then what really tips people off is not the standard symptoms of malaise, anorexia, nausea that almost any viral disease will give you, but the onset of dark urine. This precedes jaundice usually by a day or two and a lot of people will not recognize that they are jaundiced but almost everybody remembers when their urine turned to coffee.
The number of cases of hepatitis reported in the United States vary a lot from year to year. Type A hepatitis went up and then down for a long time, and now it’s back up again. Type B hepatitis, which has shown a relentless progression in the number of reported cases, despite the fact that we have an effective vaccine.
Hepatitis A is caused by a 27 nanometer RNA virus. This is a very interesting little virus, little RNA virus. It’s like the enteroviruses. It’s very closely related to the polio virus. If you look at pictures of them, the polio virus and the hepatitis A virus, they look exactly alike. What they differ in is their tissue trophism. As you know they are transmitted the same way, by the fecal/oral route. In the old days they used to say oral/fecal route but I can guarantee you it’s really fecal/oral route. And that’s the same way you get polio virus, as you get type A hepatitis virus, and it’s absorbed the same; through your intestines. It’s just that the code of the virus, the hepatitis virus, wants to go live in the liver but the code of the polio virus wants to go live.
This is the serologic course of hepatitis A. This little box represents fecal shedding of the virus. Billions and billions of virus being shed in the stool and you’ll notice that they are being shed before the patient becomes symptomatic.
How long does the IgM antibody last? This is Dr. Guff’s data from Australia and you can see that this is about 250 days, or about 2/3 of a year. Most people’s antibody response for the IgM lasts about three months.
The risk factors in the United States for hepatitis A right now - and it’s kind of surprising - look, unknown. Half of cases when people say, "How did you get this?" "Don’t know, don’t know." The things that you usually ask people questions for, travel or "Have you eaten at Taco John’s?" they are very small, relatively small areas.
So who should get hepatitis A vaccine? International travelers. My son was visiting me before he went off to Burma and so I gave him his hepatitis A vaccine sitting at the kitchen table and this is extremely useful if you can vaccinate.
The important thing to me is not that the vaccine works or that we can recognize groups of people who would benefit from this vaccine, but actually associated uses of this vaccine. I think that these are still being explored but there’s something to look forward to. For instance, right now we give immunoglobulin from outbreaks of hepatitis A which it is currently indicated.
Now we come to a much more complex disease, the hepatitis B virus. This is a 44 nanometer circular, double-stranded DNA virus. It’s the smallest DNA virus that we know of. It has a whole bunch of antigens. The surface antigen, E antigen, core and X antigen. There are all the appropriate antibodies directed at these and we’ll go through some slides to look at the serologic response to hepatitis B infection to try to understand what some of these tests mean. The epidemiology of this disease is different than hepatitis A.
I could tell you something about our liver transplant studies and that, and maybe if we get a chance we’ll go to that later.
But the chronic carrier - that was the serological happenings in someone who gets acute disease and gets over it - but the chronic carrier has a very different course. The characteristics of chronic carriers with type B hepatitis in humans is that they are surface antigen positive all the time. That’s the test. If you want to know if a person is a chronic carrier, do a surface antigen.
So how about transplantation for type B hepatitis? This is an active area right now. Very very interesting. Fulminant disease, yes we treat them with transplantation and with very good results. If they are hepatitis B virus DNA negative we think about it. If they are hepatitis B virus DNA positive, it’s very very difficult to have good outcomes.
Hepatitis, as you know, used to be a terrible problem with blood transfusions and this is a little slide to show you different cohorts from the 1960’s through the 1970’s. You can see that post-transfusion hepatitis dropped a lot, from one-third of people who were transfused by more than one unit, down to 7%.
With adults, if you become infected with type C hepatitis, the chances are at least 60% - maybe 80% - that you will become a chronic carrier of hepatitis C virus. Right now there is no prevention, and I might as well get this out of my system now: I don’t have great hopes for hepatitis C vaccine right now. The answer comes from two studies.
What is the natural history of type C hepatitis? In looking at … Leonard Seep looked at quite a few people - this was from Harvey Alter’s group, followed who got transfusion related disease at the NIH - these people didn’t die more often but they died more often of cirrhosis. And they - this was only a ten-year follow-up - they probably didn’t follow them up long enough. These were older people who usually got their disease by being operated on.
How do you get it? IV drug use, household or sexual. I have my real doubts about the plus part here. Parenteral 4%: that means blood transfusion, unknown, huge 42%. The CDC classifies this as low socioeconomic class. I guess if you have an empty wallet you get type C hepatitis.
Sexual transmission: rarely if ever transmitted by any form of sexual intercourse, and we’ve even studied this is people who have gotten transplanted for their hepatitis C, they are getting cyclosporine, they have a virus load that is 100 to thousands of times that of the average person with chronic type C hepatitis, and we found no incidence.
So let me just say, right now the accepted treatment for type C hepatitis is 3 million units, three times a week, given for one year. You can probably increase response rates and secure elimination of virus half again above the usual six-months treatment by treating for an entire year.
Hepatitis D. This is a 35 nanometer RNA virus. It’s kind of all alone in the world. It’s a satellite virus. There are plant viruses like this. But no other human virus is like this. There’s one antigen, one antibody; of course, epidemiologically what makes it so important is that it is hepatitis B virus dependent. The hepatitis B virus has been with mankind so long that the virus has developed a parasite and this disease is a parasite of the hepatitis B virus.
How about hepatitis E virus? This is a 33 nanometer single-stranded RNA virus, probably in the colici-virus family and it has one antigen, the E antigen there. This is a capital E different. And one antibody directed to it and you’ve got to think of this as a different kind of hepatitis A. Because it is caused by waterborne epidemics.